X-ray micro-tomography and its applications in whole-organism imaging and 3D histology
Open Access
- Author:
- Ding, Yifu
- Graduate Program:
- Biomedical Sciences
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- January 31, 2019
- Committee Members:
- Keith C Cheng, Dissertation Advisor/Co-Advisor
Keith C Cheng, Committee Chair/Co-Chair
Feng Yue, Committee Member
Diane M Thiboutot, Committee Member
Charles H Lang, Outside Member
Qing X Yang, Committee Member
Patrick La Riviere, Special Member - Keywords:
- zebrafish
micro-CT
3D histology
phenomics - Abstract:
- Extending histological studies to all three dimensions would be transformational for organismal and tissue phenotyping, potentially bringing increased reproducibility and replicability when compared with current approaches. However, three-dimensional histology is impractical with existing techniques, as visible light-based imaging technologies do not have the combination of field-of-view and throughput to make digital, volumetric histology tractable. To this end, the work presented in this dissertation demonstrates the use of X-ray micro-tomography in obtaining a three-dimensional histology. Multiple aspects (e.g., sample preparation, imaging geometry, processing, and data sharing) of X-ray micro-tomography are customized and expanded upon to allow for section-free, full-volume histology of millimeter scale soft tissues. Whole larval and juvenile zebrafish, chosen as the model organism due to their size and range of exhibited tissues, were reconstructed at around 1 micron voxel resolution. With a comprehensive three-dimensional histology of zebrafish in hand, the power of this approach is illustrated by phenotyping wild- type and mutant organisms. Notably, computational analysis of the reconstructed data reveals individual phenotypic variation in the brain of larval zebrafish. These analyses exemplify how three-dimensional histology via X-ray tomography, or “histo- tomography,” can offer new ways to understand the structure and organization of cells in whole organisms and tissues.